TY - JOUR A1 - Chiu, Winston A1 - Verschueren, Lore A1 - Eynde, Christel van der A1 - Buyck, Christophe A1 - De Meyer, Sandra A1 - Jochmans, Dirk A1 - Bojkova, Denisa A1 - Ciesek, Sandra A1 - Cinatl, Jindrich A1 - De Jonghe, Steven A1 - Leyssen, Pieter A1 - Neyts, Johan A1 - Loock, Marnix van A1 - Damme, Ellen van T1 - Development and optimization of a high-throughput screening assay for in vitro anti-SARS-CoV-2 activity: Evaluation of 5676 Phase 1 Passed Structures T2 - Journal of medical virology N2 - Although vaccines are currently used to control the coronavirus disease 2019 (COVID-19) pandemic, treatment options are urgently needed for those who cannot be vaccinated and for future outbreaks involving new severe acute respiratory syndrome coronavirus virus 2 (SARS-CoV-2) strains or coronaviruses not covered by current vaccines. Thus far, few existing antivirals are known to be effective against SARS-CoV-2 and clinically successful against COVID-19. As part of an immediate response to the COVID-19 pandemic, a high-throughput, high content imaging–based SARS-CoV-2 infection assay was developed in VeroE6 African green monkey kidney epithelial cells expressing a stable enhanced green fluorescent protein (VeroE6-eGFP cells) and was used to screen a library of 5676 compounds that passed Phase 1 clinical trials. Eight drugs (nelfinavir, RG-12915, itraconazole, chloroquine, hydroxychloroquine, sematilide, remdesivir, and doxorubicin) were identified as inhibitors of in vitro anti–SARS-CoV-2 activity in VeroE6-eGFP and/or Caco-2 cell lines. However, apart from remdesivir, toxicity and pharmacokinetic data did not support further clinical development of these compounds for COVID-19 treatment. KW - antiviral agents KW - coronavirus KW - SARS coronavirus Y1 - 2022 UR - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/73352 UR - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-733523 VL - 94 IS - 7 SP - 3101 EP - 3111 PB - Wiley CY - Bognor Regis [u.a.] ER -